4APH

Human angiotensin-converting enzyme in complex with angiotensin-II

Summary for 4APH

• Entry DOI: 10.2210/pdb4aph/pdb
• Related: 1O86 1O8A 1UZE 1UZF 2C6F 2C6N 2IUL 2IUX 2WXW 2X0B 2XY9 2XYD 2YDM 4AA1 4APJ
• Descriptor: ANGIOTENSIN-CONVERTING ENZYME, ANGIOTENSIN-2, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• Functional Keywords: hydrolase-hormone complex, zinc metalloprotease, metallopeptidase, hydrolase/hormone
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 2
• Total formula weight: 70710.84

Authors

Masuyer, G.,Schwager, S.L.U.,Sturrock, E.D.,Isaac, R.E.,Acharya, K.R. (deposition date: 2012-04-03, release date: 2012-10-17, Last modification date: 2023-12-20)

Primary citation

Masuyer, G.,Schwager, S.L.U.,Sturrock, E.D.,Isaac, R.E.,Acharya, K.R.
Molecular Recognition and Regulation of Human Angiotensin-I Converting Enzyme (Ace) Activity by Natural Inhibitory Peptides.
Sci.Rep., 2:717-, 2012

PubMed Abstract: Angiotensin-I converting enzyme (ACE), a two-domain dipeptidylcarboxypeptidase, is a key regulator of blood pressure as a result of its critical role in the renin-angiotensin-aldosterone and kallikrein-kinin systems. Hence it is an important drug target in the treatment of cardiovascular diseases. ACE is primarily known for its ability to cleave angiotensin I (Ang I) to the vasoactive octapeptide angiotensin II (Ang II), but is also able to cleave a number of other substrates including the vasodilator bradykinin and N-acetyl-Ser-Asp-Lys-Pro (Ac-SDKP), a physiological modulator of hematopoiesis. For the first time we provide a detailed biochemical and structural basis for the domain selectivity of the natural peptide inhibitors of ACE, bradykinin potentiating peptide b and Ang II. Moreover, Ang II showed selective competitive inhibition of the carboxy-terminal domain of human somatic ACE providing evidence for a regulatory role in the human renin-angiotensin system (RAS).

PubMed: 23056909
DOI: 10.1038/SREP00717

Experimental method

X-RAY DIFFRACTION (1.99 Å)